HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Accepted manuscript (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Algire, C. Articles by Pollak, M. PubMed PubMed Citation Articles by Algire, C. Articles by Pollak, M.

C Algire, Experimental Medicine, McGill University, Montreal, Quebec, H3T 1E7, Canada
M Zakikhani, Oncology, McGill University, Montreal, Quebec, Canada
M Blouin, Oncology, McGill University, Montreal, Quebec, Canada
J Shuai, McGill University, Montreal, Canada
M Pollak, Montreal, Canada

Correspondence: Carolyn Algire, Email: carolyn.algire{at}mail.mcgill.ca

Abstract

We investigated the effects of metformin on the growth of H59 carcinoma in C57BL/6J mice provided with either a control diet or a high energy diet previously, reported to lead to weight gain and systemic insulin resistance with hyperinsulinemia. 48 male mice were randomized into four groups: control diet, control diet + metformin, high energy diet or high energy + metformin. Following eight weeks on the experimental diets, selected groups received metformin in their drinking water. Three weeks following the start of metformin treatment, mice were injected with 0.5 x 10^6 H59 LLC1 cells and tumor growth was measured for 17 days. By day 17, tumors of mice on the high energy diet were nearly twice the volume of those of mice on the control diet. This effect of diet on tumor growth was significantly attenuated by metformin, but metformin had no effect on tumor growth of the mice on the control diet. Metformin attenuated the increased insulin receptor activation associated with the high energy diet and also led to increased phosphorylation of AMP kinase, two actions which would be expected to decrease neoplastic proliferation. These experimental results are consistent with prior hypothesis-generating epidemiological studies that suggest metformin may reduce cancer risk and improve cancer prognosis. Finally, these results contribute to the rationale for evaluation of the anti-neoplastic activity of metformin in hyperinsulinemic cancer patients.